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Bile acid-independent protection against Clostridioides difficile infection
Aguirre, Andrea Martinez Yalcinkaya, Nazli Wu, Qinglong Swennes, Alton Tessier, Mary Elizabeth Miyajima, Fabio Savidge, Tor Sorg, Joseph A
Aguirre, Andrea Martinez
Yalcinkaya, Nazli
Wu, Qinglong
Swennes, Alton
Tessier, Mary Elizabeth
Miyajima, Fabio
Savidge, Tor
Sorg, Joseph A
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2021-10-19
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Abstract
Clostridioides difficile infections occur upon ecological / metabolic disruptions to the normal colonic microbiota, commonly due to broad-spectrum antibiotic use. Metabolism of bile acids through a 7α-dehydroxylation pathway found in select members of the healthy microbiota is regarded to be the protective mechanism by which C. difficile is excluded. These 7α-dehydroxylated secondary bile acids are highly toxic to C. difficile vegetative growth, and antibiotic treatment abolishes the bacteria that perform this metabolism. However, the data that supports the hypothesis that secondary bile acids protect against C. difficile infection is supported only by in vitro data and correlative studies. Here we show that bacteria that 7α-dehydroxylate primary bile acids protect against C. difficile infection in a bile acid-independent manner. We monoassociated germ-free, wildtype or Cyp8b1-/- (cholic acid-deficient) mutant mice and infected them with C. difficile spores. We show that 7α-dehydroxylation (i.e., secondary bile acid generation) is dispensable for protection against C. difficile infection and provide evidence that Stickland metabolism by these organisms consumes nutrients essential for C. difficile growth. Our findings indicate secondary bile acid production by the microbiome is a useful biomarker for a C. difficile-resistant environment but the microbiome protects against C. difficile infection in bile acid-independent mechanisms.
Citation
Aguirre AM, Yalcinkaya N, Wu Q, Swennes A, Tessier ME, Roberts P, et al. (2021) Bile acid-independent protection against Clostridioides difficile infection. PLoS Pathogens, 17(10): e1010015. https://doi.org/10.1371/journal.ppat.1010015
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Journal article
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en
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© 2021 The Authors. Published by PLOS. This is an open access article available under a Creative Commons licence.
The published version can be accessed at the following link on the publisher’s website: https://doi.org/10.1371/journal.ppat.1010015
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1553-7366
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1553-7374
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This work was supported by R01AI116895 to J.A.S.; U01AI124290, R01AI100914, P01AI152999, R01NR013497 to T.S.; P30DK56338 to A.S. from the NIH (www.nih.gov) and a CONACYT-COECYT (https://coecytcoahuila.gob.mx/) fellowship 2017-2022 scholar/scholarship 625561/472087 to A.M.A.